Matrix metalloproteinases (MMPs) are proteolytic enzymes having high degradation activity against extracellular matrix proteins and are considered to support cell migration during cancer invasion and metastasis (Non-Patent Document No. 1). On the other hand, the results of analyses using knockout mice have suggested that MMP-2 enhances angiogenesis in tumor tissue (Non-Patent Document No. 2). Therefore, MMPs are good target molecules for developing cancer metastasis inhibitors and cancer growth inhibitors. To date, a large number of MMP inhibitors based on hydroxamic acid derivatives have been developed by pharmaceutical companies, etc.
It has been found that because of their low specificity, these conventionally developed MMP inhibitors inhibit not only their target MMP but also other MMPs in the body, thus producing unexpected side effect. For this reason, most of pharmaceutical companies have retreated from the development of MMP inhibitors. Besides, some of MMPs inhibit cancer invasion and metastasis. Therefore, if inhibitors with low specificity inhibit all MMPs, the effect of inhibition of their target MMP will be offset and, even worse, there is a possibility that cancer metastasis might be enhanced.
[Non-Patent Document No. 1]
    Werb, Z. (1997) Cell 91, 439-442[Non-Patent Document No. 2]    Ito, T. et al. (1998) Cancer Res. 58, 1048-1051